P862: A PHASE 1 FIRST-IN-HUMAN MONOTHERAPY STUDY OF ABBV-383, A BCMA × CD3 BISPECIFIC T-CELL–REDIRECTING ANTIBODY, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: Katja Weisel, Anita D’souza, David Hurd, Peter Voorhees, Raphael Teipel, Alfred Chung, Cesar Rodriguez, Sacha Tuchman, Neha Korde, Hana Safah, Orlando Bueno, Zhongling Feng, Tanya Rosenberg, Rajvineeth Kumar Pothacamury, Jeremy Ross, Shane Lee, Ziyi Jin, Chetasi Talati, Shaji Kumar, Ravi Vij
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Relapsed/refractory multiple myeloma (RRMM) has a poor prognosis, with limited treatment options in later lines. Immunotherapies targeting B-cell maturation antigen (BCMA), a plasma cell-specific biomarker, have shown promise in treating RRMM. ABBV-383 is a BCMA × CD3 bispecific T-cell–redirecting antibody whose mode of action may potentially decrease the incidence of cytokine release syndrome (CRS). ABBV-383 has shown promising activity in an ongoing phase 1 study in patients (pts) with RRMM (Voorhees et al. Blood 2022;140[suppl 1]:4401). Aims: This ongoing phase 1 study evaluates potential RP2D doses of 20, 40, and 60mg ABBV-383 Q3W; preliminary results from 40 and 60mg cohorts are analyzed. Due to sequential enrollment, the follow-up is longer in the 60 vs 40mg cohort at the overall study (Overall) data cutoff date. To adjust for this difference for the dose-level comparison, a 4-cycle (4-C) subset was analyzed for both cohorts, which included pts who completed ≥4 cycles or discontinued therapy in the first 4 cycles for any reason. Herein, we report updated results from the 40 and 60mg dose levels at the Overall and 4-C data cuts. Methods: Phase 1, dose-escalation and dose-expansion study (NCT03933735) of ABBV-383 in pts (≥18 yr) with RRMM (≥3 prior lines), ECOG PS ≤2, and eGFR ≥30 mL/min. Pts received ABBV-383 IV Q3W until disease progression/unacceptable toxicity. Results: As of August 16, 2022, a total of 174 pts were treated with ABBV-383 at all doses (40mg: n=55; 60mg: n=61). Median age was 68 yr (range, 35–92; 40mg: 68 [42–84]; 60mg: 68 [35–92]), median lines of prior therapy was 5 (range, 3–15; 40mg: 4 [3–11]; 60mg: 4 [3–12]) and 80% were triple-class refractory (40mg: 75%; 60mg: 82%). In total, 164 pts were included in the 4-C cutoff (40mg: n=45; 60mg: n=61). Baseline characteristics were similar in both cohorts and the median number of therapy cycles was 4 (range, 1–4) in both. At Overall cutoff, median follow-up (range) was 3.7 m (0.9–26.0) for 40mg and 15.9 m (1.1–24.9) for 60mg cohorts. At 4-C cutoff, median follow-up was 2.8 m (0.7–3.6) for 40mg and 2.8 m (0.6–13.0) for 60mg cohorts. At Overall cutoff, TEAEs were reported in 100% of pts in 40mg (G≥3 in 64% [n=35]) and 60mg (G≥3 in 80% [n=49]) cohorts. Zero (0%) and 1 (2%) pt (G4 thrombocytopenia) had a DLT during dose escalation at 40 and 60mg dose levels, respectively. Three (5%) pts at 40mg dose level and 8 (13%) at 60mg discontinued due to TEAEs. CRS occurred in 38 (69%; G≥3: n=0) pts in 40mg and 43 (70%; G≥3: n=1) in 60mg cohorts; median time to onset was 1 d (range, 1–2) for both cohorts, and median time to resolution was 2 d (1–7) and 1 d (1–10), respectively. At 4-C cutoff, TEAEs occurred in 100% of pts in 40mg (G≥3 in 62% [n=28]) and 60mg (G≥3 in 62% [n=38]) cohorts. Two (4%) pts at 40mg dose level and 4 (7%) at 60mg discontinued due to TEAEs. CRS occurred in 32 (71%; G≥3: n=0) pts in 40mg and 43 (70%; G≥3: n=1) in 60mg cohorts. Clinical responses are shown in the Table. Pharmacodynamic analyses at both dose levels showed rapid and transient increases in proinflammatory cytokines and a reduction in soluble BCMA levels over time that were associated with disease response. Summary/Conclusion: ABBV-383 monotherapy is associated with a manageable safety profile at doses of 40 and 60mg, with low incidence of TEAEs leading to discontinuation. CRS was predictable and resolved quickly with standard supportive care. Promising efficacy of ABBV-383 monotherapy was observed, with similar ORR in 40 (58%) and 60mg (61%) cohorts. These results in heavily pretreated pts with RRMM support further clinical evaluation.Keywords: Multiple myeloma, Clinical trial, Bispecific